Pulmonary lesions in Wegener's granulomatosis: a clinicopathologic study of 22 autopsy cases

Pulmonary lesions in 22 autopsy cases of Wegener's granulomatosis (WG) were studied clinicopathologically, with special emphasis on the relation of the lesions to systemic vasculitis, glomerular changes, and clinical manifestations. The pulmonary lesions were divided, on the basis of morphologic characteristics, into four types: 1) the fulminant type, which was characterized by diffusely distributed acute exudative and proliferative alveolitis with prominent small vessel vasculitis (three cases); 2) the granulomatous type, the classic granulomatous lesion (seven cases); 3) the fibrous scar type (five cases); and 4) the mixed type, which had features of both acute exudative and scar-type lesions (seven cases). Clinically, lesions of the fulminant type had rapidly deteriorating courses, terminating in respiratory failure immediately following the onset of the pulmonary manifestations, whereas those of the fibrous scar type had protracted courses. The systemic vasculitis and glomerular lesions in the cases of the fulminant type were almost exclusively fresh lesions. In contrast, the systemic lesions in the cases of the fibrous scar type were nearly always cicatricial. Thus, the morphologic features of the systemic lesions and the clinical profile in each case were well correlated with the pathologic classification of the pulmonary lesions. This correlation may support the assumption that the respiratory tract lesion plays an important role in the progression of systemic involvement in the disease. A comparative study of vascular lesions in various organs revealed some histologic differences between vasculitis in the lungs and that observed outside the respiratory tract; pathogenetic heterogeneity was thus suggested between lesions in the two locations.     

Collagen diseases with pulmonary involvement]

Pulmonary involvement is a common feature in patients with various collagen diseases. Some types of the pulmonary involvement are resistant to currently available treatment regimens and thus considered as intractable conditions. These include acute/subacute interstitial pneumonia in dermatomyositis, pulmonary interstitial fibrosis in scleroderma, and diffuse alveolar hemorrhage. Acute/subacute interstitial pneumonia with the histology of diffuse alveolar damage (DAD) is mainly occurred in patients with amyopathic or hypomyopathic dermatomyositis who lack autoantibodies to aminoacyl tRNA synthetases. Intensive immunosuppressive treatment in the early phase of the disease may be effective for this intractable complication. Nearly one-third of patients with scleroderma have slowly progressive pulmonary interstitial fibrosis, leading to end-stage respiratory failure. Non-specific interstitial pneumonia (NSIP) with an excessive fibrotic change is a major histology of these patients. There are accumulating evidences showing the effectiveness of cyclophosphamide in patients with this intractable condition, especially those with active alveolitis. Diffuse alveolar hemorrhage is a fatal complication mainly occurred in patients with systemic lupus erythematosus and those with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, including microscopic polyangitis (MPA) and Wegener's granulomatosus. Immediate diagnosis and introduction of intensive treatment are necessary to save the patients with this complication.     

Pauci-immune crescentic glomerulonephritis

Pauci-immune crescentic glomerulonephritis (PICGN) is a rapidly progressive condition leading to renal failure within days or weeks and is potentially life threatening. Majority of these patients have clinical or pathological evidence of systemic vasculitis. PICGN may occur as renal limited disease or as a component of systemic necrotising small vessel vasculitis. Majority of these cases are attributed to Wegener's granulomatosis (WG), microscopic polyangitis (MPA) or Churg Strauss syndrome (CSS). Renal involvement is encountered in 80 to 90% cases of WG and MPA and in about 45% cases of CSS. Approximately 80 to 90% patients of untreated WG or MPA and about 60% cases of CSS are positive for anti-neutrophilic cytoplasmic antibodies (ANCA). These diseases are therefore also called as ANCA-associated vasculitis. Serial ANCA measurements provide useful information on disease activity. Renal transplant should be avoided in patients with clinical evidence of active vasculitis. Even though the treatment with oral corticosteroids and i.v. or oral cyclophosphamide results in complete long term remission in 70 to 75% patients, relapse occurs in >25% cases within a mean period of 18 months after cessation of therapy. Prognosis of untreated ANCA-associated PICGN is poor.     

A case of aortic and mitral valve involvement in granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) (Wegener’s) is a necrotizing systemic vasculitis of the small-sized blood vessels, affecting kidneys, lungs, upper respiratory tract and skin. Cardiac valvular involvement is an uncommon manifestation of GPA. We report the case of a 60-year-old woman with arthritis and lung nodules due to GPA without antineutrophil cytoplasmic antibodies (ANCA) at time of diagnosis. Remission was obtained with cyclophosphamide and corticosteroid. Azathioprine was then prescribed for 2 years. Four years later, she developed severe inflammatory aortic and mitral valvular involvement characterized by GPA typical histopathological valvular lesions. Search for ANCA was positive at this time (anti-myeloperoxidase). Cardiac valvular involvement is a rare and potentially fatal complication of GPA and may misleadingly suggest infectious endocarditis. A review of literature revealed few cases of histologically well-documented cardiac valvular involvement in GPA. Pathologists should be aware of valvular heart diseases in GPA, which usually comprise valvular necrotic lesions without any microbial agents.     

Pulmonary capillaritis and hemorrhage in patients with systemic vasculitis

Thirteen patients with prominent pulmonary signs and symptoms had pulmonary capillaritis and extensive hemorrhage demonstrated by open-lung biopsy or autopsy. Vasculitis was demonstrated in other organs before or after the lung biopsy or at autopsy. Although there were several suspected causes for the pulmonary capillaritis and different final clinicopathologic diagnoses, the histopathologic features in the lung were similar in all cases and distinctive enough to separate capillaritis from other causes of hemorrhagic lung. All patients were treated with prednisone or cyclophosphamide, or both. Six patients died of their vasculitis, five in respiratory failure and one in renal failure. None of the seven survivors had a clinical recrudescence of pulmonary hemorrhage. By extrapolation from these 13 cases, one may histopathologically recognize pulmonary capillaritis when it causes hemorrhagic lung in a patient without clinically evident extrapulmonary vasculitis. One can then proceed to investigate the patient and possibly determine the nature of the vasculitis.     

Clinical Features and Outcomes of Microscopic Polyangiitis in Korea

Microscopic polyangiitis (MPA) is a systemic vasculitis affecting small vessels. To determine the clinical features and outcomes of MPA in Korean patients, we retrospectively reviewed the medical records of patients diagnosed with MPA at a single medical center in Korea between 1989 and 2006. The 18 patients who met the Chapel Hill criteria for MPA had a mean (±SD) age at the time of diagnosis of 62.4±12.7 yr. Renal manifestations and general symptoms were the most common features of MPA, with lung involvement also very common. Antineutrophil cytoplasmic antibodies (ANCA) were present in 17 of the 18 patients (94%). Of 17 patients treated with steroids and cyclophosphamide, 11 (65%) had stable or improved course. One patient treated with steroids without cyclophosphamide showed disease progression. Ten of the 18 patients (56%) died at a median follow-up of 8 months. MPA in Korean patients was distinguished by a higher rate of lung involvement, especially alveolar hemorrhage, which was the leading cause of death in our patients. Korean patients were also older at MPA onset and were more likely positive for ANCA. Other overall clinical manifestations did not differ significantly.     

SARS肺的病理鉴别诊断

目的 分析严重急性呼吸综合征(severe acute respiratory syndrome，SARS)肺部病变的临床病理形态学特征及与其他肺部炎性疾病的鉴别诊断。方法 对3例行尸体解剖的SARS病例的肺组织进行组织形态学、免疫组织化学和电镜下超微结构的观察，对其临床表现、病理形态学特征及主要鉴别诊断进行探讨，并与病理资料完整的16例病毒性肺炎、13例间质性肺炎的肺部病变进行鉴别诊断。结果 死亡的SARS病人肺部病变主要表现为弥漫性的肺部损伤，但是各处病变轻重不一。肺泡腔内可见细颗粒样或泡状水肿液，其中可见脱落的肺泡上皮细胞。肺泡间隔表面可见透明膜覆盖，有的区域肺泡腔内出现机化性改变，肺泡腔和肺问质内可见大量的巨噬细胞浸润。同时，肺间质内的小动脉壁出现明显的损伤性改变。结论 SARS的肺部病理形态学特征可与其他肺部炎症性疾病鉴别。     

Antineutrophil cytoplasmic antibody(ANCA)

ANCA are associated with small sized vessel vasculitis; one subtype is an antibody against myeloperoxidase(MPO), which stains in a perinuclear pattern(P-ANCA) indirect immunofluorescence(IIF) using a neutrophil substrate, and the other subtype is an antibody against proteinase-3(PR-3), which stains in a diffuse granular cytoplasmic pattern ANCA by IIF. PR-3 ANCA is more specific in Wegener's granulomatosis(WG) than the other primary vasculitides. MPO-ANCA can be found in microscopic polyangiitis (MPA), Churg Strauss Syndromes(CSS), drug-induced vasculitis, and environmental factor-induced such as silicosis vasculitis more frequently than WG. The value of the IIF test for ANCA detection can be greatly increased by the addition of a standardized antigen-specific ELISA. The intra-assay and inter-assay CV of the MPO and PR-3 ELISA were 6.6 to 4.8%, respectively. Close ANCA titer correlation was shown between MPO-ANCA ELISA and the activity of ANCA associated vasculitis. Renal manifestations and pulmonary manifestations are observed in 70-90% of AAV as the initial manifestation. The changes in titers of ANCA seem to reflect disease activity in 60-70% of AAV patients. A combination of steroids and immunosuppressive drugs is effective in relieving the clinical symptoms of AAV.     

从SARS患者肺部病变的病理特点探讨SARS的损伤机理

目的 根据严重急性呼吸道综合征(severe acute respiratory syndrome，SARS)患者肺部病变的病理特点探讨SARS的损伤机理。方法 在3500例尸体解剖材料中，找出死亡时有肺部炎症的共842例。对其中病毒性肺炎16例、Good-Pasture综合征2例、自身免疫疾病2例、SARS1例，共21例进行肺部病变的病理组织学的比较观察。结果 病毒性肺炎的肺部病变主要的病理变化表现为间质性肺炎；自身免疫性疾病病人的肺部病理变化有肺泡表面透明膜形成，肺泡腔内脱落的细胞团，肺泡腔内机化等；SARS病人尸体解剖的肺部病变主要为肺泡腔内细颗粒样或泡状肺水肿，脱屑性肺炎以及机化性肺炎的表现。同时，肺间质内的小动脉出现明显的结构改变，形态学上与自身免疫性疾病的肺损伤相似。结论 机体的变态反应可能是SARS的损伤机理之一。     

The clinical pathology of severe acute respiratory syndrome (SARS): a report from China

In order to investigate the clinical pathology of severe acute respiratory syndrome (SARS), the autopsies of three patients who died from SARS in Nan Fang Hospital Guangdong, China were studied retrospectively. Routine haematoxylin and eosin (H&E) staining was used to study all of the tissues from the three cases. The lung tissue specimens were studied further with Macchiavello staining, viral inclusion body staining, reticulin staining, PAS staining, immunohistochemistry, ultrathin sectioning and staining, light microscopy, and transmission electron microscopy. The first symptom was hyperpyrexia in all three cases, followed by progressive dyspnoea and lung field shadowing. The pulmonary lesions included bilateral extensive consolidation, localized haemorrhage and necrosis, desquamative pulmonary alveolitis and bronchitis, proliferation and desquamation of alveolar epithelial cells, exudation of protein and monocytes, lymphocytes and plasma cells in alveoli, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells. There was also massive necrosis of splenic lymphoid tissue and localized necrosis in lymph nodes. Systemic vasculitis included oedema, localized fibrinoid necrosis, and infiltration of monocytes, lymphocytes, and plasma cells into vessel walls in the heart, lung, liver, kidney, adrenal gland, and the stroma of striated muscles. Thrombosis was present in small veins. Systemic toxic changes included degeneration and necrosis of the parenchyma cells in the lung, liver, kidney, heart, and adrenal gland. Electron microscopy demonstrated clusters of viral particles, consistent with coronavirus, in lung tissue. SARS is a systemic disease that injures many organs. The lungs, immune organs, and systemic small vessels are the main targets of virus attack, so that extensive consolidation of the lung, diffuse alveolar damage with hyaline membrane formation, respiratory distress, and decreased immune function are the main causes of death.     

严重急性呼吸综合征病原体检测及临床病理学观察

目的 研究重症急性呼吸综合征(SARS)的临床病理学特点。方法 利用3例尸检材料为观察对象,全部材料经常规HE染色,肺组织部分标本经组织化学Macchiavello法(病毒包涵体染色)、网状纤维、PAS染色;免疫组织化学;超薄切片及染色;光镜及透射电镜观察。结果 3例均以高热为首发症状,继而出现进行性呼吸困难和肺部阴影;肺部病变：双肺广泛性实变;灶性出血,坏死,脱屑性肺泡炎及支气管炎,肺泡腔内充满增生脱落的肺泡上皮及渗出的蛋白、单核细胞、淋巴细胞和浆细胞,肺透明膜形成,部分肺泡腔内、渗出物机化呈肾小球样机化性肺炎改变,肺泡上皮细胞内可见病毒包涵体;免疫器官损伤：脾脏淋巴组织大片状坏死,淋巴结灶性坏死。骨髓造血组织抑制;全身小血管炎：心、肺、肝、肾、肾上腺、横纹肌间小静脉周围及血管壁水肿,灶性纤维素样坏死,单核细胞、淋巴细胞浸润,部分小静脉有血栓形成;全身中毒性改变：肺、肝、肾、心、肾上腺实质细胞变性,坏死。肺组织透射电镜观察发现群集的病毒颗粒。结论本病是一种全身多器官损伤性疾病,肺部及免疫系统是病毒主要作用的靶器官,肺部广泛性实变,大量透明膜形成,呼吸窘迫及免疫功能低下是本病死亡的主要原因。     

Antineutrophil cytoplasmic autoantibody in the absence of Wegener's granulomatosis or microscopic polyangiitis: implications for the surgical pathologist.

Antineutrophil cytoplasmic antibodies (ANCA) are useful serologic markers for the diagnosis and management of patients with Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). However, problems in diagnosis and classification may occur when patients with other disorders develop ANCA. A 7-year review (1993-1999) disclosed 247 patients whose sera tested positively for ANCA by an indirect immunofluorescence method: 166 patients for cytoplasmic-ANCA (C-ANCA) and 81 patients for perinuclear-ANCA (P-ANCA) Twenty-seven patients had active pulmonary disease and underwent open-lung biopsy or transbronchial biopsy. Eight patients (30%) had a disease other than WG or MPA, and their clinical, pathological, and serological findings were reviewed. The patients, all women, ranged in age from 28 to 77 years (median, 37 y). Dyspnea (n = 6), cough (n = 6), chest pain (n = 2), and/or hemoptysis (n = 2) were present. The duration of symptoms lasted from 3 weeks to 6 years (median, 6 mo). ANCA titers were C-ANCA (n = 4; range, 1:40-1280) or P-ANCA (n = 4; range, 1:40-640). The lung biopsies disclosed nonspecific interstitial pneumonia (n = 4), bronchiolitis obliterans organizing pneumonia (n = 1), diffuse alveolar damage (n = 1), organizing diffuse alveolar hemorrhage without capillaritis (n = 1), and necrotic granuloma (n = 1). No cases showed characteristic histology for WG or MPA. The final diagnoses were various connective tissue disorders (n = 5), chronic hypersensitivity pneumonia (n = 1), postinfectious bronchitis/bronchiectasis (n = 1), and ulcerative colitis-related lung disease (n = 1). Surgical pathologists should be aware that significantly elevated ANCA titers may be associated with diverse forms of pulmonary disease. ANCA positivity alone, in the absence of appropriate clinical or pathologic findings, should not be used to substantiate a diagnosis of WG or MPA.     

Transbronchial biopsy in the diagnosis of sarcoidosis and certain other interstitial lung diseases

Results of transbronchial pulmonary biopsy studies of patients of different sex and age suffering from interstitial pulmonary lesion are presented. Different diagnostic value of transbronchial pulmonary biopsy (TBBP) is shown in relation to different lesions. In case of sarcoidosis its informative value, for example, is high, while in the diffuse processes such as cryptogenic fibrosing alveolitis, the data allow only suggestive diagnosis and recommendation of an open lung biopsy. In chronic nonspecific pulmonary diseases TBBP helps to clarify the character and the activity of the process involved. In some cases it is possible to reveal a latent cancer. It is suggested to use the term "allergic alveolitis" (indicating the mechanism of development of changes mentioned) when such changes as alveolitis, small granulemas and intraalveolar outgrowths are found in the biopsy specimens.     

Antineutrophil cytoplasmic antibodies (ANCA)

Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80–90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10–20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10–20% of patients with WG or MPA (and 40–50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear.

ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.     

Antineutrophil cytoplasmic antibodies (ANCA)

Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80-90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10-20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear. ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.     

Histological diversity of vasculitic lesions in MPO–ANCA-positive autopsy cases

To investigate the variety of histological features of vasculitic lesions in myeloperoxidase-specific antineutrophil cytoplasmic antibody (pANCA)-related vasculitis, retrospective pathological analysis was done on 13 autopsy cases, collected from 1990 to 1998 at five hospitals. These cases were classified into three groups: (i) pulmonary-renal syndrome characterized by capillaritis of lung and glomeruli with occasional small-vessel arteritis and/or phlebitis; (ii) glomerular capillaritis without pulmonary involvement associated with significant small-vessel arteritis; and (iii) extensive distribution of small-vessel arteritis with no capillary involvement. The results suggest that pANCA-related vasculitis encompasses a wide variety of vasculitic syndromes, including pulmonary-renal syndrome, microscopic polyarteritis nodosa, and classic polyarteritis nodosa. pANCA may contribute to pathogenesis in all of these cases.     

Audit of the clinical usefulness of a rapid qualitative ELISA screen for antimyeloperoxidase and antiproteinase 3 antibodies in the assessment of patients with suspected vasculitis

BACKGROUND: The need for urgent antineutrophil cytoplasmic antibody (ANCA) results when assessing patients with acute renal failure, pulmonary renal syndrome, or mononeuritis multiplex has led to the development of a rapid qualitative ELISA screening assay for antibodies to myeloperoxidase (MPO) and proteinase 3 (PR3). AIMS: To report the use of a rapid qualitative ELISA screen for PR3-ANCA and MPO-ANCA in a regional immunology laboratory and its correlation with standard indirect immunofluorescence (IIF) and quantitative ELISA for PR3-ANCA and MPO-ANCA. METHODS: Over 12 months, 103 samples requiring urgent ANCA testing were screened by a rapid qualitative ELISA and the results compared with IIF and quantitative ELISA assays for PR3-ANCA and MPO-ANCA. RESULTS: There was an excellent correlation between the rapid qualitative ELISA and standard ANCA IIF and a routine ELISA for MPO/PR3-ANCA, with sensitivities ranging from 82% to 100%. There were two false negatives, which gave weak to moderately positive values as determined by routine ELISA. However, the clinical relevance of these two cases is doubtful. CONCLUSIONS: The rapid ELISA for anti-MPO and anti-PR3 correlates well with quantitative ELISA and IIF ANCA, and urgent management decisions in patients with suspected small vessel vasculitis can be based with confidence on this test.     

Pulmonary edema and hemorrhage, possible causes of pulmonary infection and respiratory failure in the early stage of lower spinal cord injury

Pulmonary infection and respiratory failure are frequently encountered in the early stage of acute spinal cord injury (SCI) and are thought of as the chief causes of death. Unfortunately, there is little knowledge concerned with the pathogenesis of pulmonary infection, respiratory failure and other pathological changes in the lung in the early stage of SCI. Pulmonary embolism, respiratory muscle dysfunction, poor expectoration caused by position, and decreased ability to cough up respiratory secretions were the main causes. These explanations may be beyond criticism in high-level paraplegia in SCI, but are unconvincing in lower SCI such as in low-thoracic cord injury where the phenomenon of pneumonia and respiratory dysfunction remains. There might be some more important factors that lead to pulmonary infection and respiratory failure in the early stage of SCI. In SCI rats, pulmonary edema and hemorrhage were occurred in the early stage of SCI while the other organs were almost normal. And the location of lung edema and hemorrhage were the same as that of pulmonary infection. The purpose of this paper is to propose pathological changes in the lung and possible causes for pulmonary infection and respiratory failure. We hypothesize that pulmonary edema and hemorrhage in the early stage of SCI might be the chief factor contributing to pulmonary infection and respiratory failure in lower SCI.     

Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis.

Anti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21 sera from patients with acute systemic vasculitis following incubation with normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive binding assays using F(ab')2 fragments from IVIg and affinity chromatography of ANCA IgG on Sepharose-bound F(ab')2 fragments from IVIg. Co-incubation of sera from patients with acute systemic vasculitis with paired autologous remission stage sera also resulted in inhibition of ANCA activity in acute sera. Remission sera contain IgM and IgG capable of interacting with beta and or alpha idiotypes of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of expression of ANCA activity in whole serum from patients in remission from systemic vasculitis, which were found to contain high titres of ANCA IgG. These observations suggest that remission of systemic vasculitis is associated with the generation of anti-idiotypes against autoantibodies rather than the suppression of production of ANCA autoantibodies. IVIg may modulate the activity of systemic vasculitis in vivo.     

The diagnosis and classification of microscopic polyangiitis

Microscopic Polyangiitis (MPA) is a small vessel vasculitis. The disease is defined by the 2012 revised Chapel Hill Consensus Conference Nomenclature of Vasculitides [1] as necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels (i.e. capillaries, venules, or arterioles). Necrotizing arteritis involving small and medium arteries may be present. Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs. Granulomatous inflammation is absent. MPA belongs to the ANCA-associated vasculitides (AAV). ANCA in MPA are predominantly directed against myeloperoxidase (MPO-ANCA) but may, in a minority of patients, be directed against proteinase 3 (PR3-ANCA). Not all patients, however, have ANCA. Microscopic polyangiitis (MPA) belongs to the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. MPA is clinically characterized by small-vessel vasculitis primarily affecting the kidneys and the lungs but other organs may be involved as well. Renal involvement, which can be the only manifestation, is clinically apparent as rapidly progressive glomerulonephritis and histopathologically as pauci-immune necrotizing and crescentic glomerulonephritis. ANCA in MPA are mainly directed to myeloperoxidase (MPO-ANCA). Besides their diagnostic significance, MPO-ANCA appear pathogenic in MPA. Rituximab with steroids is at least as effective as cyclophosphamide with steroids for induction of remission.